Search PubMed⌕ Search

Biomedical subjects

S M Feinstone

Publications and source records attributed to S M Feinstone.

At least 91 records · Page 5Linked to original sources
PubMed1983

Inactivation of hepatitis B virus and non-A, non-B hepatitis by chloroform.

To determine whether a non-A, non-B hepatitis agent contained essential lipids, we extracted with chloroform a dilution of human plasma that contained approximately 10(4) chimpanzee infectious doses of non-A, non-B hepatitis virus and then tested for infectivity in chimpanzees. In addition, we treated a serum containing hepatitis B virus in the same way. Both of these samples were also sham extracted as controls. Known chloroform-sensitive and chloroform-resistant viruses were added directly to the hepatitis-containing serum or plasma as internal controls or to fetal calf serum as external controls and were assayed for infectivity in vitro after chloroform extraction or sham extraction. All infectivity of the diluted plasma that contained at least 10(4) chimpanzee infective doses of non-A, non-B hepatitis agent and all infectivity of the serum that contained 10(3.5) chimpanzee infective doses of hepatitis B virus were destroyed by chloroform. The chloroform-sensitive control viruses were completely inactivated, but the chloroform-resistant control viruses lost less than 0.5 log10 of infectivity. Sham-extracted non-A, non-B hepatitis agent-containing plasma was shown to maintain its infectivity in chimpanzees that had initially been inoculated with the chloroform-extracted plasma. Thus, both hepatitis type B and non-A, non-B hepatitis appear to be caused by viruses that can be inactivated by a lipid solvent.

Animals↗
PubMed1983

Taxonomic classification of hepatitis A virus.

Sufficient data have accumulated to permit the ICTV Ad Hoc Study Group on the Taxonomy of Hepatitis Viruses to recognize hepatitis A virus as a picornavirus. Within the family Picornaviridae, hepatitis A virus closely resembles members of the genus Enterovirus.

Enterovirus↗
PubMed1983

Live attenuated vaccine for hepatitis A.

The successful development of hepatitis B vaccines has stimulated interest in the active immunoprophylaxis of type A hepatitis. The development of hepatitis A vaccines has been simplified by the ability to propagate HAV in tissue culture systems and the availability of animal model systems, including the chimpanzee and certain species of marmosets in which to evaluate safety and efficacy of candidate vaccines. Both inactivated and live, attenuated hepatitis A vaccines are possible, but the limited replicative ability of HAV in tissue culture makes the former impractical at present. However, HAV appears to be rapidly attenuated by serial passage in tissue culture and such attenuated strains are candidates for a live, attenuated vaccine similar to the Sabin polio vaccine. The HM-175 strain of HAV, recovered from the stool of a patient with type A hepatitis in Melbourne, Australia, was isolated directly in primary African green monkey kidney (AGMK), a cell substrate suitable for vaccine development. This strain has been serially passaged over 20 times in AGMK. The parent strain (stool extract) and virus at tissue culture passages 10 and 20 were evaluated for infectivity and virulence in seronegative chimpanzees. The parent strain produced evidence of liver damage (elevated liver enzymes) at all dilutions of infectious virus tested. In contrast, tissue culture-passaged virus was fully infectious for chimpanzees, but did not produce biochemical evidence of hepatitis. Similarly, hepatitis A viral antigen could not be detected in liver biopsies and little or no viral antigen could be detected in acute phase stool samples.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1981

Serodiagnosis of viral hepatitis A by a solid-phase radioimmunoassay specific for IgM antibodies.

A solid-phase radioimmunoassay for detecting specific IgM antibodies to hepatitis A virus (HAV) was developed and characterized. The test utilized microtiter plates coated with anti-IgM to specifically absorb the IgM antibodies from the test serum. The anti-hepatitis A IgM antibodies are measured by the specific consecutive binding of hepatitis A antigen and radiolabelled anti-hepatitis A antibodies (anti-HA). In 6 chimpanzees infected with HAV, IgM anti-HA was detected from about the first date of elevated transaminases and was positive for about 3 months. The usefulness of the test was confirmed by testing acute phase sera of 30 patients from a common source outbreak of epidemic hepatitis, and negative sera from 2 control groups. A collection of serum specimens from 190 patients with sporadic HBsAg-negative hepatitis in Brazil was also tested and an etiologic association with HAV was confirmed in the majority of these cases.

Alanine Transaminase↗
PubMed1981

Non-A, non-B hepatitis in chimpanzees and marmosets.

Nine of 15 specimens of human origin thought to contain non-A, non-B hepatitis agents caused hepatitis in recipient chimpanzees. Two have been further characterized. One inoculum, designated strain F, has been reported to produce unique cytoplasmic changes detected by electron microscopy in liver biopsy specimens; the other, strain H, produced distinctive nuclear changes. It is not yet clear whether these two changes result from infection by different agents; they have been useful markers of non-A, non-B hepatitis in chimpanzees. Strain F was serially passaged six times in chimpanzees, and the infectivity titer of the strain F plasma was estimated to be less than 10(2)/ml. Strain H had an infectivity titer in chimpanzees of at least 10(6)/ml. Both the strain F and strain H agents have been successfully transmitted and serially passaged in marmosets. Although hepatitis was detected in a lower percentage of marmosets than chimpanzees given either the strain F or H inoculum, the infectivity titer of the strain H agent appeared to be greater than or equal to 10(8) marmoset infectious doses/ml.

Acute Disease↗
PubMed1981

Propagation of human hepatitis A virus in African green monkey kidney cell culture: primary isolation and serial passage.

Human hepatitis A virus (HAV) was propagated in primary African Green Monkey (Cercopithecus aethiops) kidney (AGMK) cell cultures. Three strains of HAV were used: MS-1, SD-11, and HM-175. Cells were inoculated with marmoset-passaged material or human clinical specimens and were stained by direct immunofluorescence to establish the identity of the virus. Both clinical samples and marmoset-passaged material produced immunofluorescence. HAV antigen was found scattered throughout the cytoplasm of inoculated cultures. The HM-175 strain produced the most intense immunofluorescence. This strain of HAV had been serially passaged in cell culture seven times. Blocking experiments with paired human sera from naturally acquired HAV infections and hyperimmune chimpanzee serum from an experimentally infected animal established that the immunofluorescence was specific. The viral antigen was found to be exclusively intracellular. The interval to maximum HAV antigen expression was decreased by serial passage. The HAV strain described herein, which was recovered directly from the stool specimen of a patient with HAV in primary AGMK cell culture, may prove useful as a source of antigen for serological tests and as a candidate vaccine strain.

Animals↗
PubMed1980

Detection of antibodies to single-stranded DNA in naturally acquired and experimentally induced viral hepatitis.

A sensitive "Farr" assay, utilizing 125I-labelled DNA was developed for detecting antibody to single-stranded DNA (anti-ssDNA). The test was shown to be specific and as sensitive as assays using 14C-labelled DNA, for the detection of antibody in patients with connective tissue diseases. Groups of sera from patients with naturally acquired viral hepatitis and experimentally infected chimpanzees were tested for anti-ssDNA by the 125I assay and by counterimmunoelectrophoresis (CIEP). No consistent pattern was observed with either technique, indicating the elevated levels of this antibody are not as reliable markers of parenchymal liver damage as had been previously suggested.

Animals↗
PubMed1980

Hepatitis A virus in the liver and intestine of marmosets after oral inoculation.

A total of 12 seronegative marmosets (Saguinus mystax) were inoculated orally with hepatitis A virus (HAV) and sacrificed at 3- to 4-day intervals. Tissues from the livers, intestines, mesenteric lymph nodes, and spleens were obtained for immunofluorescence studies, and bile and intestinal contents were obtained for enzyme-linked immunosorbent assay studies. Two marmosets sacrificed on days 34 and 41 after inoculation developed antibody to HAV and demonstrated HAV in their livers but not in any part of their intestinal tissues. None of the remaining marmosets sacrificed from days -3 to 31 survived long enough to develop antibody to HAV, but an additional two marmosets, which were sacrificed on days 21 and 31, demonstrated HAV in their livers and also in bile but not in the intestinal tissues or their contents. The mesenteric lymph nodes and spleens were negative for HAV by immunofluorescence in all the marmosets. No evidence of HAV replication was demonstrated in any part of the intestine at any time during the incubation period or during acute illness in the marmosets inoculated orally with HAV. The shedding of HAV in stools in the late incubation period can be explained by excretion of HAV from the livers with the bile.

Alanine Transaminase↗
PubMed1980

PLC/PRF/5 (Alexander) hepatoma cell line: further characterization and studies of infectivity.

The Alexander hepatoma cell line, PLC/PRF/5, was studied for evidence of hepatitis B virus markers and alpha-fetoprotein. Only hepatitis B surface antigen and alpha-fetoprotein were detected. Induction experiments with 5-iodo-2'-deoxyuridine and inoculation of chimpanzees with whole cells or tissue culture fluid did not reveal evidence of synthesis of additional hepatitis B virus markers or of production of infectious virus.

Animals↗
PubMed1979

Non-A, non-B hepatitis: ultrastructural evidence for two agents in experimentally infected chimpanzees.

Two different ultrastructural alterations were observed in liver cells of chimpanzees inoculated with plasma derived from two different patients with non-A, non-B hepatitis. During the acute phase of illness in one group of four chimpanzees, peculiar tubular structures, composed of two unit membranes with electron-opaque material in between, were observed in the cytoplasm of hepatocytes. In contrast, these structures were never detected in the liver cells of the second group of five chimpanzees that received the second inoculum, However, nuclear changes, usually associated with aggregates of 20- to 27-nanometer particles, were found in hepatocytes of the latter animals. Although these particles resembled viruses, they were not as uniform as small virus particles often appear. In five other chimpanzees inoculated with non-A, non-B hepatitis material not known to be related to the first two inocula, cytoplasmic structures were found in four, and nuclear structures were found in the remaining one. Thus, all 14 chimpanzees inoculated with transmissible non-A, non-B hepatitis agents could be classified as having either nuclear or cytoplasmic changes. These observations add support to epidemiologic data suggesting that there may be more than one agent of non-A, non-B hepatitis.

Animals↗
PubMed1979

Circulating immune complexes in non-A, non-B hepatitis. Possible masking of viral antigen.

Serial serum samples from 22 patients with transfusion-associated non-A, non-B hepatitis and 2 chimpanzees with the experimentally induced disease were tested for circulating immune complexes by Raji-cell radioimmunoassay. 13 patients (59%) and 1 chimpanzee had circulating immune complexes immediately before, coincident with, or during the return to normal of raised aminotransferase activity. 7 of the 10 patients with chronic non-A, non-B hepatitis had detectable complexes at levels which waxed and waned in parallel with changes in serum aminotransferase activity. Immune complexes may contain and mask viral antigens, and their presence may explain the failure of conventional immunological techniques to detect virus antigens.

Acute Disease↗
PubMed1978

Enzyme-linked immunosorbent assay for detection of hepatitis A antigen in stool and antibody to hepatitis A antigen in sera: comparison with solid-phase radioimmunoassay, immune electron microscopy, and immune adherence hemagglutination assay.

Previously described techniques for detection of hepatitis A antigen (HA Ag) and antibody (anti-HA) have required purified HA Ag and expensive equipment. Herein is described an enzyme-linked immunosorbent assay (ELISA) for specific detection of HA Ag in human stool filtrates and of anti-HA in sera by using selected HA Ag-containing human stool filtrates as the antigen source. Because human stools often react nonspecifically in serological tests for HA Ag, blocking with preexposure and hyperimmune anti-HA sera from a chimpanzee inoculated with hepatitis A virus was used to confirm specific detection of HA Ag. The sensitivity of ELISA was found to be comparable to that of solid-phase radioimmunoassay (SPRIA) and immune electron microscopy (IEM). Of 37 acute-phase stools collected from nine patients, 16 were positive for HA Ag by ELISA. In 13 of these, HA Ag particles were found by IEM, and an additional 3 stools negative by ELISA contained HA Ag particles by IEM. Eight control stools were negative by both ELISA and IEM. Anti-HA was measured in sera by demonstrating its ability to block binding of the enzyme conjugate to HA Ag in a stool without detectable nonspecificity. This test (blocking ELISA) was as sensitive and specific as blocking SPIRA, IEM, and immune adherence hemagglutination and, like SPRIA and IEM, detected early-developing antibody. The ELISA is simple to perform and requires only a minimum of equipment. It is useful for screening stools for HA Ag and for monitoring HA Ag during purification, as well as for detecting early and late anti-HA in sera.

Acute Disease↗